Low-intensity ultrasound induces angiogenesis in rat hind-limb ischemia

Barzelai, Sharon; Sharabani-Yosef, Orna; Holbová, Radka; Castel, David; Walden, Raphael; Engelberg, S; Scheinowitz, Mickey

doi:10.1016/j.ultrasmedbio.2005.08.010

Cited by 75 publications

(62 citation statements)

References 26 publications

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“…Neovascularization is thought to be the result of hematopoietic stem cells and endothelial progenitor cell activity. The results of our study indicated that there were more blood vessels in LIPUS-treated limbs, which is in accordance with results of a previous study [3]. The enhanced neovascularization suggests that LIPUS can increase the activity of hematopoietic stem cells and improve local blood perfusion.…”

Section: Discussionsupporting

confidence: 92%

“…Therefore, a valid treatment is imperative for preventing collapse of the femoral head and subsequent osteoarthritis. Several studies have reported that LIPUS can enhance bone repair and local blood flow in animal models [3,16,24,34]. However, whether the effect of osteogenesis and neovascularization by LIPUS can enhance the repair progress in steroid-associated osteonecrosis is unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Fivemicron sections were cut and stained with hematoxylin and eosin for evaluation of osteonecrosis and calculation of fat cell size. The a-smooth muscle actin (a-SMA) staining was used to assess the number and mean diameter of blood vessels [2,3]. The undecalcified samples were fixed in 70% ethanol solution at 4°C for 2 days, embedded in methylmethacrylate, and cut into 10-lm slices.…”

Section: Histologic Evaluation and Immunohistochemistrymentioning

confidence: 99%

“…The mean of the two sections from each sample was taken as the value of that sample. The following parameters were assessed: (1) 200 osteocyte lacunae were counted in each established field at 9 200 magnification and then the percentage of the empty osteocyte lacunae was determined [33]; (2) the average diameter of the fat cells was measured in each field and the average diameter for fat cells of each animal was determined [26,33]; (3) the number and diameter of blood vessels were measured and averaged for each sample based on the a-SMA staining slides [3]. The number of blood vessels was expressed per area of tissue (/mm 2 ); (4) the mineralizing surface and bone surface and mineral apposition rate (lm/day) were calculated as described in previous studies [6,35].…”

Section: Histologic Evaluation and Immunohistochemistrymentioning

confidence: 99%

“…In vitro studies have shown that LIPUS increases bone formation, osteoblast activity, and osteogenic differentiation of mesenchymal stem cells (MSCs) [27,31]. In vivo studies have found that LIPUS treatment promotes new bone formation and improves tissue blood flow [3,16,24,34]. Rutten et al [29], in a clinical study, showed that LIPUS accelerates fracture healing through increased osteoblast activity.…”

Section: Introductionmentioning

confidence: 99%

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Low-intensity Pulsed Ultrasound Enhances Bone Repair in a Rabbit Model of Steroid-associated Osteonecrosis

Zhu

Cai

Lin

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Background Steroids are a leading cause of femoral head osteonecrosis. Currently there are no medications available to prevent and/or treat steroid-associated osteonecrosis. Low-intensity pulsed ultrasound (LIPUS) was approved by the FDA for treating delayed union of bone fractures. Some studies have reported that LIPUS can enhance bone formation and local blood flow in an animal model of fracture healing. However, whether the effect of osteogenesis and neovascularization by LIPUS can enhance the repair progress in steroid-associated osteonecrosis is unknown.Questions/purposes We hypothesized that LIPUS may facilitate osteogenesis and neovascularization in the reparative processes of steroid-associated osteonecrosis. Using a rabbit animal model, we asked whether LIPUS affects (1) bone strength and trabecular architecture; (2) blood vessel number and diameter; and (3) BMP-2 and VEGF expression. Methods Bilateral femoral head necrosis was induced by lipopolysaccharide and methylprednisolone in 24 rabbits. The left femoral heads of rabbits received LIPUS therapy (200 mW/cm 2 ) for 20 minutes daily and were classified as the LIPUS group. The right femoral heads of the same rabbits did not receive therapy and were classified as the control group. All rabbits were euthanized 12 weeks after LIPUS therapy. Micro-CT, biomechanical testing, histologic evaluation, immunohistochemistry, quantitative realtime PCR, and Western blot were used for examination of the effects of LIPUS. Results Twelve weeks after LIPUS treatment, the loading strength in the control group was 355 ± 38 N (95% CI, 315-394 N), which was lower (p = 0.028) than that in the LIPUS group (441 ± 78 N; 95% CI, 359-524 N). The bone tissue volume density (bone volume/total volume) in the LIPUS group (49.29% ± 12.37%; 95 % CI, 36.31%-62.27%) was higher (p = 0.022) than that in the control group (37.93% ± 8.37%; 95 % CI, 29.15%-46.72%). The percentage of empty osteocyte lacunae in the LIPUS group (17% ± 4%; 95% CI, 15%-20%) was lower (p = 0.002) than that in the control group (26% ± 9%; 95% CI, 21%-32%). The mineral apposition rate (lm/day) in the LIPUS group (2.3 ± 0.8 lm/day; 95% CI, 1.8 2.8 lm/day) was higher (p = 0.001) than that in the control group (1.6 ± 0.3 lm/day; 95% CL, 1.4-1.8 lm/day). The number of blood vessels in the LIPUS group (7.8 ± 3.6/mm 2 ; 95% CI, 5.5-10.1 mm 2 ) was greater (p = 0.025) than the number in Hanxiao Zhu and Xunzi Cai contributed equally to this work and should be considered as co-first authors.The institution of the authors has received funding from the National Natural Science Foundation of China (Hangzhou, Zhejiang, China) (81101377, 81101345, 81171687, 81371954, 81201414, 81201416, 81401785, 81472113) 123Clin Orthop Relat Res (2015) 473:1830-1839 DOI 10.1007 Clinical Orthopaedics and Related Research ® A Publication of The Association of Bone and Joint Surgeons® the control group (5.7 ± 2.6/mm 2 ; 95% CI, 4.0-7.3 mm 2 ). Messenger RNA (mRNA) and protein expression of BMP-2 in the LIPUS group (75 ± 7, 95% CI, 70-7...

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Section: Discussionsupporting

confidence: 92%